Chemoreceptors play a major homeostatic role during hemorrhage, shock, hypoxia, and acidosis, yet the mechanism which causes the chemoreceptors to discharge remains unknown. Local hypoxia, pH, pCO2, acetylcholine, dopamine and K ion have all been implicated. Measurements of the PO2 in the carotid body of the cat with our micro O2 electrode suggest that hypoxia in the classical sense is not responsible for the discharge, but the possibility has not been eliminated. We will make additional measurements of carotid body PO2 in vivo and in vitro at several levels of discharge of the chemoreceptors in a further attempt to test the hypoxia theory, as well as to determine the threshold PO2 for sensor discharge and its relationship to arterial PO2. Oxygen consumption will be determined from disappearance curves of O2 and from A-V difference and flow in order to assess the metabolic cost of discharge, and the role of metabolic factors in the excitation process. The use of a multi-barrelled microelectrode will permit simultaneous measurements of PO2, local blood flow, and electrical activity (membrane potentials, generator and/or action potentials?). Local injections and electrical stimulation are also possible. In some experiments an additional microelectrode will be used to probe for concommittent electrical activity in the surround. The possible release of transmitter substances will be also assessed using two excised, superfused carotid bodies in series. The influence of arterial (and local) pH, pCO2 and PO2, chemicals and hormones, on chemoreceptor discharge and the other measured parameters will be assessed. Histological studies will be carried out to determine the location of the electrode tip, not only to determine the extent of possible tissue damage, but possibly to identify and characterize the receptor. These studies are expected to yield valuable information not only on chemoreceptor discharge but also on carotid body metabolism which appears to have some unique features.